US4112236A
Expired / Lapsed
US
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Interphenylene 8-aza-9-dioxothia-11,12-secoprostaglandins
Assignee: Merck and Co Inc
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Filing: 1977-04-04
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Granted: 1978-09-05
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Expires: 1997-04-04
Abstract
Abstract Interphenylene 8-aza-9-dioxothia-11,12-secoprostaglandins are prepared by the two-stage alkylation of the anion of a lower alkyl sulfonamide, R 1 SO 2 NH 2 , using first a compound of the formula: ##STR1## and second, a compound of the formula: ##STR2## The compounds produced have renal vasodilatory activity when administered orally and are therefore useful for treating patients with renal impairment.
Inventors
- 👤 John B. Bicking
- 👤 Edward J. Cragoe, Jr.
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-11-05 07:48
CPC Classifications
C; C07; C07D; C07D309/00; C07D309/02; C07D309/08; C07D309/10; C07D309/12; C07C; C07C29/00; C07C29/132; C07C29/136; C07C29/143; C07C45/00; C07C45/004; C07C49/00; C07C49/76; C07C49/80
Claims Analysis
Total Claims: 29
Claim 1
Independent Claim
199 words
The compound having the following formula: ##STR26## wherein R is carboxy, a pharmaceutically acceptable carboxy salt, or alkoxycarbonyl of the formula --COOR 5 wherein R 5 is alkyl of 1-10 carbon atoms; A is (CH 2 ) n wherein n is 0 or 2, or oxymethylene or vinylene; Y is (CH 2 ) n wherein n is 1, 3, or 4, provided that the sum of chain-forming elements in A and Y is either 3 or 4; R 1 is lower alkyl of 1-4 carbon atoms; Z is ethylene, vinylene, or ethynylene; R 2 is hydrogen or methyl; R 3 is hydrogen or methyl; and R 4 is lower alkyl of 3-6 carbon atoms straight or branched or 3-butenyl, provided that in one instance wherein R 4 is lower alkyl and R 2 is methyl, R 4 and R 2 are joined together with abstraction of hydrogen to form a carbocyclic ring of form 6-9 members, and further provided that in one instance when R 4 is lower alkyl and R 2 is hydrogen, R 4 and the carbon bearing R 2 and OH are joined with abstraction of hydrogen to form a carbocyclic ring of from 5-8 members.
Claim 2
Dependent Claim
199 words
The compound having the following formula: ##STR26## wherein R is carboxy, a pharmaceutically acceptable carboxy salt, or alkoxycarbonyl of the formula --COOR 5 wherein R 5 is alkyl of 1-10 carbon atoms; A is (CH 2 ) n wherein n is 0 or 2, or oxymethylene or vinylene; Y is (CH 2 ) n wherein n is 1, 3, or 4, provided that the sum of chain-forming elements in A and Y is either 3 or 4; R 1 is lower alkyl of 1-4 carbon atoms; Z is ethylene, vinylene, or ethynylene; R 2 is hydrogen or methyl; R 3 is hydrogen or methyl; and R 4 is lower alkyl of 3-6 carbon atoms straight or branched or 3-butenyl, provided that in one instance wherein R 4 is lower alkyl and R 2 is methyl, R 4 and R 2 are joined together with abstraction of hydrogen to form a carbocyclic ring of form 6-9 members, and further provided that in one instance when R 4 is lower alkyl and R 2 is hydrogen, R 4 and the carbon bearing R 2 and OH are joined with abstraction of hydrogen to form a carbocyclic ring of from 5-8 members.
Claim 3
Dependent Claim
32 words
The compound of claim 1 wherein R is carboxy or a carboxy salt, --COO - M + wherein M + is a pharmaceutically acceptable cation derived from a metal or an amine.
Claim 4
Dependent Claim
69 words
The compound of claim 2 which has the formula: ##STR27## wherein A is (CH 2 ) n wherein n is 0 or 2, or oxymethylene or vinylene; Y is (CH 2 ) n wherein n is 1, 3, or 4; R 1 is lower alkyl of 1-4 carbon atoms; Z is ethylene, vinylene, or ethynylene; R 3 is hydrogen or methyl; and R 4 is lower alkyl or 3-butenyl.
Claim 5
Dependent Claim
25 words
The compound of claim 3 wherein A is (CH 2 ) o , Y is (CH 2 ) 3 , and R 3 is hydrogen.
Claim 6
Dependent Claim
9 words
The compound of claim 4 wherein Z is ethylene.
Claim 7
Dependent Claim
17 words
4-{3-[N-(4-Hydroxynonyl)methanesulfonamido]-propyl}benzoic acid, the compound of claim 5 wherein R 1 is methyl and R 4 is butyl.
Claim 8
Dependent Claim
17 words
4-{3-[N-(4-Hydroxynonyl)ethanesulfonamido]-propyl}benzoic acid, the compound of claim 5 wherein R 1 is ethyl and R 4 is butyl.
Claim 9
Dependent Claim
17 words
4-{3-[N-(4-Hydroxyundecyl)methanesulfonamido]-propyl}benzoic acid, the compound of claim 5 wherein R 1 is methyl and R 4 is hexyl.
Claim 10
Dependent Claim
17 words
4-{3-[N-(4-Hydroxy-8-nonenyl)methanesulfonamido]propyl}benzoic acid, the compound of claim 5 wherein R 1 is methyl and R 4 is 3-butenyl.
Claim 11
Dependent Claim
17 words
4-{3-[N-(8,8-Dimethyl-4-hydroxynonyl)-methanesulfonamido]propyl}benzoic acid, the compound of claim 5 wherein R 1 is methyl and R 4 is 3,3-dimethylbutyl.
Claim 12
Dependent Claim
9 words
The compound of claim 4 wherein Z is vinylene.
Claim 13
Dependent Claim
17 words
4{3-[N-(4-Hydroxy-2-nonenyl)methanesulfonamido]propyl}benzoic acid, the compound of claim 11 wherein R 1 is methyl and R 4 is butyl.
Claim 14
Dependent Claim
28 words
The compound of claim 3 wherein A is (CH 2 ) o , Y is (CH 2 ) 3 , R 3 is methyl, and Z is ethylene.
Claim 15
Dependent Claim
17 words
4-{3-[N-(5,5-Dimethyl-4-hydroxynonyl)-methanesulfonamido]propyl}benzoic acid, the compound of claim 13 wherein R 1 is methyl and R 4 is butyl.
Claim 16
Dependent Claim
22 words
The compound of claim 3 wherein A is oxymethyl, Y is CH 2 , R 3 is hydrogen, and Z is ethylene.
Claim 17
Dependent Claim
17 words
{4-[N-(4-Hydroxynonyl)methanesulfonamidomethyl]phenoxy}acetic acid, the compound of claim 15 wherein R 1 is methyl and R 4 is butyl.
Claim 18
Dependent Claim
81 words
The compound of claim 2 which has the formula: ##STR28## wherein A is (CH 2 ) n wherein n is 0 or 2, or oxymethylene, or vinylene; Y is (CH 2 ) n wherein n is 1, 3, or 4, and A and Y are in the ortho, meta, or para orientation; R 1 is lower alkyl of 1-4 carbon atoms; Z is ethylene, vinylene, or ethynylene; R 3 is hydrogen or methyl; and R 4 is lower alkyl or 3-butenyl.
Claim 19
Dependent Claim
47 words
4-{3-[N-(4-Hydroxy-4-methylnonyl)methanesulfonamido]propyl}benzoic acid, the compound of claim 17 wherein A is (CH 2 ) o , Y is (CH 2 ) 3 , and A and Y are in the para orientation, R 1 is methyl, Z is ethylene, R 3 is hydrogen, and R 4 is butyl.
Claim 20
Dependent Claim
76 words
The compound of claim 2 which has the formula: ##STR29## wherein A is (CH 2 ) n wherein n is 0 or 2, or oxymethylene or vinylene; Y is (CH 2 ) n wherein n is 1, 3, or 4, and A and Y are in the ortho, meta, or para orientation; R 1 is lower alkyl or 1-4 carbon atoms; Z is ethylene, vinylene, or ethynylene; and n is an integer of 2 to 6.
Claim 21
Dependent Claim
42 words
4-{3-[N-(3-(1-Hydroxycyclohexyl)-2-propynyl)methanesulfonamido]propyl}benzoic acid, the compound of claim 19 wherein A is (CH 2 ) o , Y is (CH 2 ) 3 , and A and Y are in the para orientation, R 1 is methyl, Z is ethynylene, and n is 3.
Claim 22
Dependent Claim
42 words
4-{3-[N-(3-(1-Hydroxycyclohexyl)propyl)-methanesulfonamido]propyl}benzoic acid, the compound of claim 19 wherein A is (CH 2 ) o , Y is (CH 2 ) 3 , and A and Y are in the para orientation, R 1 is methyl, Z is ethylene, and n is 3.
Claim 23
Dependent Claim
157 words
The compound of claim 2 which has the formula ##STR30## wherein A is (CH 2 ) n wherein n is 0 or 2, or oxymethylene or vinylene; Y is (CH 2 ) n wherein n is 1, 3, or 4; R 1 is lower alkyl of 1-4 carbon atoms; Z is ethylene, vinylene or ethynylene; R 2 and R 3 are independently hydrogen or methyl; and R 4 is lower alkyl of 3-6 carbon atoms and 3-butenyl; provided that in one instance wherein R 4 is lower alkyl and R 2 is methyl, R 4 and R 2 are joined together with abstraction of hydrogen to form a carbocyclic ring of from 6-9 members, and further provided that in one instance when R 4 is lower alkyl and R 2 is hydrogen, R 4 and the carbon bearing R 2 and OH are joined with abstraction of hydrogen to form a carbocyclic ring of from 5-8 members.
Claim 24
Dependent Claim
35 words
m-[N-(4-Hydroxynonyl)methanesulfonamidomethyl]cinnamic acid, the compound of claim 22 wherein A is vinylene, Y is CH 2 , R 1 is methyl, Z is ethylene, R 2 and R 3 are hydrogen, and R 4 is butyl.
Claim 25
Dependent Claim
39 words
m-[N-(4-Hydroxynonyl)methanesulfonamidomethyl]hydrocinnamic acid, the compound of claim 22 wherein A is (CH 2 ) 2 , Y is CH 2 , R 1 is methyl, Z is ethylene, R 2 and R 3 are hydrogen, and R 4 is butyl.
Claim 26
Dependent Claim
156 words
The compound of claim 2 which has the formula: ##STR31## A is (CH 2 ) n wherein n is 0 or 2, or oxymethylene or vinylene; Y is (CH 2 ) n wherein n is 1, 3, or 4; R 1 is lower alkyl of 1-4 carbon atoms; Z is etnylene, vinylene or ethynylene; R 2 and R 3 are independently hydrogen or methyl; and R 4 is lower alkyl of 3-6 carbon atoms and 3-butenyl; provided that in one instance wherein R 4 is lower alkyl and R 2 is methyl, R 4 and R 2 are joined together with abstraction of hydrogen to form a carbocyclic ring of from 6-9 members, and further provided that in one instance when R 4 is lower alkyl and R 2 is hydrogen, R 4 and the carbon bearing R 2 and OH are joined with abstraction of hydrogen to form a carbocyclic ring of from 5-8 members.
Claim 27
Dependent Claim
41 words
2-{4-[N-(4-Hydroxynonyl)methanesulfonamido]-butyl}benzoic acid, the compound of claim 25 wherein A is (CH 2 ) o , Y is (CH 2 ) 4 , R 1 is methyl, Z is ethylene, R 2 and R 3 are hydrogen, and R 4 is butyl.
Claim 28
Dependent Claim
165 words
The compound of claim 1 which has the formula: ##STR32## wherein R 5 is alkyl of 1-10 carbon atoms; A is (CH 2 ) n wherein n is 0 or 2, or oxymethylene or vinylene; Y is (CH 2 ) n wherein n is 1, 3, or 4; R 1 is lower alkyl of 1-4 carbon atoms; Z is ethylene, vinylene or ethynylene; R 2 and R 3 are independently hydrogen or methyl; and R 4 is lower alkyl of 3-6 carbon atoms and 3-butenyl; provided that in one instance wherein R 4 is lower alkyl and R 2 is methyl, R 4 and R 2 are joined together with abstraction of hydrogen to form a carbocyclic ring of from 6-9 members, and further provided that in one instance when R 4 is lower alkyl and R 2 is hydrogen, R 4 and the carbon bearing R 2 and OH are joined with abstraction of hydrogen to form a carbocyclic ring of from 5-8 members.
Claim 29
Dependent Claim
54 words
Methyl 4-{3-[N-(4-Hydroxynonyl)methanesulfonamido]propyl}benzoate, the compound of claim 27 wherein R 5 is methyl, A is (CH 2 ) o , Y is (CH 2 ) 3 , and A and Y are in the para orientation, R 1 is methyl, Z is ethylene, R 2 and R 3 are hydrogen, and R 4 is butyl.
References Cited (Backward Citations)
GB1429092A
Cited
US3991106A
Cited
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1981-09-04 | 1982-03-06 | 1982-09-05 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1985-09-04 | 1986-03-06 | 1986-09-05 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1989-09-04 | 1990-03-06 | 1990-09-05 | $7700.00 | Window Closed / Lapsed |